Effectiveness and Safety of Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C

Hepatitis C, Chronic Clinical Trial

— C-DIAMOND  

Official title:

Effectiveness and Safety of Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C: Multi-center, Prospective, Observational Real-world Study in EASTERN China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04952207
• Other study ID #: IN-CN-342-5424
• Status: Recruiting
• Start date: March 6, 2019
• Est. completion date: August 31, 2021

Study information

• Verified date: July 2021
• Source: Ruijin Hospital
• Contact: Qing Xie, MD
• Phone: 008613651804273
• Email: xieqingrjh[@]163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Clinical trials evaluating DAA have shown excellent rates of SVR and good safety profiles in patients with CHC infection. Real world data from TARGET, TRIO, IFI, DHCR, DALTON-C, as well as those cohorts from Japan, Taiwan and Korea further confirmed clinical trial findings of DAA in routine practice where populations are more complex. However, these populations are different from Chinese for different host and virus characteristics which limit the applicability of results to local practice.

As DAA launched in China since 2017, the availability of INF free DAA treatment will likely lead to better treatment outcome in routine practice, but there are currently no data available to test the hypothesis.

In clinical practice, the uptake of DAA regimen will depend on a combination of physician preference, patient's characteristics and drug access. This study will also identify how these three variables affect DAA regimen uptake.

This study to 1) characterize pts receiving IFN free DAA regimens, 2) represent common practice in China, 3) describe outcome of various INF free DAA therapy, and 4) confirm registration study results.

Description:

Chronic Hepatitis C (hereinafter referred to as "CHC") is a viral hepatitis caused by the infection of Hepatitis C virus (HCV). In 2007, a cross-sectional study in six cities showed that the prevalence of HCV was 0.58% in China. It was estimated that there were about 10 million HCV patients in our country. If hepatitis C was not treated in time, about 75% of patients would progress into chronic hepatitis C six months after virus infection; the probability was 5%~15% for progression into cirrhosis and 2%~4% for progression into hepatocellular carcinoma 20 years after the infection of chronic hepatitis C. One analysis of cirrhosis etiology in northern China found that the proportion of CHC-induced cirrhosis was increased from 6.39% in 2002 to 13.91% in 2011.

As a result of the severely epidemiological burden of CHC, the World Health Organization (WHO) has established a target to eliminate the hepatitis harm in 2030 ("2030 global targets" for short) that 90% reduction in new cases of chronic hepatitis B and C in 2030, 80% of treatment-eligible people with chronic hepatitis B and C treated and 65% reduction in hepatitis B and C deaths. As a part of the strategy to achieve this target, WHO includes the treatment with direct-acting antiviral agents (DAAs) into the 2017 Essential Medicine List. In addition, the Viral Hepatitis Prevention and Control Programs in China (2017-2020) also emphasize the application of more effective treatment as a part of the strategy to reduce the transmission of HCV.

Direct-acting antiviral agents (DAAs) are a new drug for the treatment of CHC now. In 2017, China Food and Drug Administration (CFDA)/ National Medical Products Administration (NMPA) approved the marketing of Sofosbuvir of Gilead, Ombitasvir/Paritaprevir/Ritonavir Tablets + Dasabuvir of AbbVie, Daclatasvir Tablets + Asunaprevir Capsules of Bristol-Myers Squibb; Elbasvir/Grazoprevir of MSD, Sofosbuvir/Velpatasvir and Ledipasvir/Sofosbuvir of Gilead and Danoprevir of Ascletis in 2018. Before the DAAs are marketed, the pegylated interferon combined with ribavirin (PR) therapy is the major therapy of antiviral for HCV-infected patients. However, the real-world study showed that the sustained virological response (SVR) of PR therapy was 71.1%. The DAAs therapy was demonstrated with shorter treatment time, better efficacy, fewer adverse events, and higher compliance compared with the PR therapy.

Multiple clinical trials indicated a high SVR rate and safety of DAAs in CHC patients. The real-world studies with more complicated patient populations, including TARGET, TRIO, IFI, DHCR, and DALTON-C as well as the cohort studies from Japan, Taiwan, and the Republic of Korea also further demonstrated good clinical efficacy with DAAs. While GT 1-3 is prevalent worldwide, subtypes of 1b, 2a, 3a, 3b, and 6a are prevalent in China, and among them, GT 3 and 6 are expanding. Since the host and virus characteristics of these populations are different from the Chinese population, the BMI of the Chinese population is smaller than that of the European and American population, IL28 CC GT is predominant, and HCV patients of GT 3b is most common among HCV patients of GT 3. So, it is necessary to further demonstrate the applicability of the results of these studies to Chinese patients.

DAAs have been marketed in China since 2017. The treatment with DAAs unnecessary to combine with any interferon (IFN) may obtain better therapeutic effect in clinical practice. However, there is a lack of real-world data to verify this hypothesis now.

In clinical practice, the selection of therapy with DAAs will depend on the physician preference, patient baseline characteristics, and drug accessibility. This study will also determine the baseline status of patients receiving different DAA treatments and possible reasons for doctors' prescriptions in the real world.

In the eastern part of China, the GTs of HCV infected patients are GT 1b (69.2%), GT 2a (20.8%), GT 3a (2.2%), GT 3b (4.4%) and GT 6 (3.2%).To demonstrate whether DAAs provide good efficacy and safety to the patients, including the patients with cirrhosis, accompanying with infection, kidney/liver transplantation, or no response to PR therapy, the purpose of this study is to 1) describe the patient characteristics for DAA therapy unnecessary to combine with any IFN in routine clinical practice in China; 2) describe the therapeutic effect of multiple DAAs unnecessary to combine with any IFN to verify above hypothesis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: August 31, 2021
• Est. primary completion date: July 31, 2021
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All Chronic hepatitis C patients to be treated with the DAAs approved by CFDA/NMPA

• Age=18 years

Exclusion Criteria:

• Patients experienced with DAAs

• Documented HCC, AFP>500ng/ml

• Unlikely to survive 1 year or inability to participate and follow up for the study period

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Direct-acting antiviral agents
The initial DAA treatment and its dose for all patients is determined by the infectionist or hepatologist based on the clinical diagnosis and treatment routine. The administration dose in the instructions for use for current DAAs marketed in China Mainland unnecessary to combine with any IFN is shown but not limited as follows: Sofosbuvir, Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir, Daclatasvir, Asunaprevir, Elbasvir/Grazoprevir, Sofosbuvir/Velpatasvir and Ledipasvir/Sofosbuvir.

Locations

Country	Name	City	State
China	Changzhou Third People's Hospital	Changzhou	Jiangsu
China	The First Hospital of Jiaxing	Jiaxing	Zhejiang
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	The Second Hospital of Nanjing	Nanjing	Jiangsu
China	Hwa Mei Hospital	Ningbo	Zhejiang
China	Huashan Hospital	Shanghai	Shanghai
China	Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai	Shanghai
China	The Fifth People's Hospital of Suzhou	Suzhou	Jiangsu
China	Wuxi No. 5 People's Hospital	Wuxi	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
Qing XIe	Gilead Sciences, Tigermed Consulting Co., Ltd

Country where clinical trial is conducted

China, 

References & Publications (9)

Chen Y, Yu C, Yin X, Guo X, Wu S, Hou J. Hepatitis C virus genotypes and subtypes circulating in Mainland China. Emerg Microbes Infect. 2017 Nov 1;6(11):e95. doi: 10.1038/emi.2017.77. — View Citation

Chen YS, Li L, Cui FQ, Xing WG, Wang L, Jia ZY, Zhou MG, Gong XH, Wang FZ, Zheng H, Luo HM, Bi SL, Wang N, Yang WZ, Liang XF. [A sero-epidemiological study on hepatitis C in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2011 Sep;32(9):888-91. Chinese. — View Citation

Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16. — View Citation

Heo YA, Deeks ED. Sofosbuvir/Velpatasvir/Voxilaprevir: A Review in Chronic Hepatitis C. Drugs. 2018 Apr;78(5):577-587. doi: 10.1007/s40265-018-0895-5. Review. — View Citation

Lu J, Zhou Y, Lin X, Jiang Y, Tian R, Zhang Y, Wu J, Zhang F, Zhang Y, Wang Y, Bi S. General epidemiological parameters of viral hepatitis A, B, C, and E in six regions of China: a cross-sectional study in 2007. PLoS One. 2009 Dec 24;4(12):e8467. doi: 10.1371/journal.pone.0008467. — View Citation

Lu L, Nakano T, He Y, Fu Y, Hagedorn CH, Robertson BH. Hepatitis C virus genotype distribution in China: predominance of closely related subtype 1b isolates and existence of new genotype 6 variants. J Med Virol. 2005 Apr;75(4):538-49. — View Citation

Matthews SJ, Lancaster JW. Telaprevir: a hepatitis C NS3/4A protease inhibitor. Clin Ther. 2012 Sep;34(9):1857-82. doi: 10.1016/j.clinthera.2012.07.011. Epub 2012 Aug 28. Review. — View Citation

Ogawa E, Furusyo N, Murata M, Hayashi T, Shimizu M, Mukae H, Toyoda K, Hotta T, Uchiumi T, Hayashi J. Impact of HCV kinetics on treatment outcome differs by the type of real-time HCV assay in NS3/4A protease inhibitor-based triple therapy. Antiviral Res. 2016 Feb;126:35-42. doi: 10.1016/j.antiviral.2015.12.001. Epub 2015 Dec 12. — View Citation

Rao HY, Li H, Chen H, Shang J, Xie Q, Gao ZL, Li J, Sun Y, Jiang J, Wang L, Zhao L, Zhang L, Yang W, Niu J, Gong Z, Gong G, Yang R, Lee MH, Wei L. Real-world treatment patterns and clinical outcomes of HCV treatment-naive patients in China: an interim analysis from the CCgenos study. J Gastroenterol Hepatol. 2017 Jan;32(1):244-252. doi: 10.1111/jgh.13467. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SVR12 rate of DAA	Sustained virological response at 12 week; ie, HCV RNA <15 IU/ ml at 12 weeks after the treatment with DAA regimen.	12 weeks after the treatment with DAA regimen